1. Field of Invention
The present invention relates to a strategy for combating the tendency of bioprosthetic material to calcify in vivo.
2. Description of Related Art
Pathologic calcification has limited the use of prostheses that incorporate tissue components. In relation to such “bioprotheses,” U.S. Pat. No. 5,674,298 to Levy et al. discusses the problem and one approach to its solution, which entails pretreating a bioprosthetic tissue with a polyphosphonate:polyepoxide monoadduct. The polyepoxide serves to stabilize the bioprosthetic tissue against subsequent in vivo enzymatic degradation by crosslinking with collagen chains of the tissue. While effective for stabilization, the polyepoxide promotes calcification but the polyphosphonate provides chelating oxygen atoms that can counteract the calcification.
The solution advanced in the Levy patent has drawbacks, however. After the pretreatment, the anti-calcification effect on the bioprosthetic material gradually wanes, possibly because the effective agent, the polyphosphonate, is washed out over time. To the extent that polyphosphonates bind tissues covalently, a possibility raised by Levy et al., the anti-calcification efficiency of the polyphosphonates may be impaired because the binding is achieved by partial alkylation of their chelating oxygen atoms, which would disable the function of the chelating oxygen atoms to block the growth of calcium crystals. Applying more polyphosphonates to compensate could affect adversely the crosslinking between the polyepoxide and the prosthetic tissue.
Published international application PCT/US01/58503 discloses another approach that entails the use of crosslinking triglycidyl amine (TGA) to achieve improved calcification resistance for bioprosthetic materials. For instance, TGA treatment has been employed to inhibit in vivo calcification of the valve cusp component in a porcine aortic valve bioprosthesis.
The TGA-crosslinking methodology falls short, however, in the inhibition of calcification in certain parts of a bioprosthetic heart valve. In particular, it is relatively ineffective against calcification of the aortic wall segment of a bioprosthetic implant. It also is less effective at inhibiting bovine pericardial calcification.